CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001225
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Low-density lipoprotein receptor-related protein 6 
Protein Synonyms/Alias
 LRP-6 
Gene Name
 LRP6 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
941TFLLFSQKSAINRMVubiquitination[1]
977IDYDPLDKQLYWIDSubiquitination[2]
1403RMLCPRMKGDGETMTubiquitination[3]
1443LPGMSRGKSMISSLSubiquitination[4, 5]
1477SSSSSSTKGTYFPAIubiquitination[5]
1554MTSVATAKGYTSDLNubiquitination[2, 4, 5]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor- ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3- mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity). 
Sequence Annotation
 REPEAT 63 106 LDL-receptor class B 1.
 REPEAT 107 149 LDL-receptor class B 2.
 REPEAT 150 193 LDL-receptor class B 3.
 REPEAT 194 236 LDL-receptor class B 4.
 REPEAT 237 276 LDL-receptor class B 5.
 DOMAIN 282 324 EGF-like 1.
 REPEAT 372 414 LDL-receptor class B 6.
 REPEAT 415 457 LDL-receptor class B 7.
 REPEAT 458 501 LDL-receptor class B 8.
 REPEAT 502 542 LDL-receptor class B 9.
 REPEAT 543 584 LDL-receptor class B 10.
 DOMAIN 588 628 EGF-like 2.
 REPEAT 674 716 LDL-receptor class B 11.
 REPEAT 717 759 LDL-receptor class B 12.
 REPEAT 760 802 LDL-receptor class B 13.
 REPEAT 803 842 LDL-receptor class B 14.
 REPEAT 843 885 LDL-receptor class B 15.
 DOMAIN 889 930 EGF-like 3.
 REPEAT 977 1025 LDL-receptor class B 16.
 REPEAT 1026 1068 LDL-receptor class B 17.
 REPEAT 1069 1113 LDL-receptor class B 18.
 REPEAT 1114 1156 LDL-receptor class B 19.
 REPEAT 1157 1198 LDL-receptor class B 20.
 DOMAIN 1203 1244 EGF-like 4.
 DOMAIN 1248 1286 LDL-receptor class A 1.
 DOMAIN 1287 1323 LDL-receptor class A 2.
 DOMAIN 1325 1361 LDL-receptor class A 3.
 REGION 20 275 Beta-propeller 1.
 REGION 328 589 Beta-propeller 2.
 REGION 631 890 Beta-propeller 3.
 REGION 933 1202 Beta-propeller 4.
 MOTIF 1487 1493 PPPSP motif A.
 MOTIF 1527 1534 PPPSP motif B.
 MOTIF 1568 1575 PPPSP motif C.
 MOTIF 1588 1593 PPPSP motif D.
 MOTIF 1603 1610 PPPSP motif E.
 MOD_RES 1420 1420 Phosphoserine; by CK1.
 MOD_RES 1430 1430 Phosphoserine; by CK1.
 MOD_RES 1479 1479 Phosphothreonine.
 MOD_RES 1490 1490 Phosphoserine; by CDK14, GRK5 and GRK6.
 MOD_RES 1493 1493 Phosphothreonine; by CK1.
 LIPID 1394 1394 S-palmitoyl cysteine.
 LIPID 1399 1399 S-palmitoyl cysteine.
 CARBOHYD 42 42 N-linked (GlcNAc...) (Potential).
 CARBOHYD 81 81 N-linked (GlcNAc...) (Potential).
 CARBOHYD 281 281 N-linked (GlcNAc...) (Potential).
 CARBOHYD 433 433 N-linked (GlcNAc...) (Potential).
 CARBOHYD 486 486 N-linked (GlcNAc...) (Potential).
 CARBOHYD 692 692 N-linked (GlcNAc...).
 CARBOHYD 859 859 N-linked (GlcNAc...).
 CARBOHYD 865 865 N-linked (GlcNAc...).
 CARBOHYD 926 926 N-linked (GlcNAc...).
 CARBOHYD 1039 1039 N-linked (GlcNAc...).
 DISULFID 286 297 By similarity.
 DISULFID 293 308 By similarity.
 DISULFID 310 323 By similarity.
 DISULFID 592 603 By similarity.
 DISULFID 599 612 By similarity.
 DISULFID 614 627 By similarity.
 DISULFID 893 904
 DISULFID 900 914
 DISULFID 916 929
 DISULFID 1207 1218
 DISULFID 1214 1228
 DISULFID 1230 1243
 DISULFID 1249 1263 By similarity.
 DISULFID 1256 1276 By similarity.
 DISULFID 1270 1285 By similarity.
 DISULFID 1288 1300 By similarity.
 DISULFID 1295 1313 By similarity.
 DISULFID 1307 1322 By similarity.
 DISULFID 1326 1338 By similarity.
 DISULFID 1333 1351 By similarity.
 DISULFID 1345 1360 By similarity.
 CROSSLNK 1403 1403 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Complete proteome; Developmental protein; Disease mutation; Disulfide bond; EGF-like domain; Endocytosis; Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix; Ubl conjugation; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1613 AA 
Protein Sequence
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF 60
SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE 120
VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFIIINSE 180
IYWPNGLTLD YEEQKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT 240
DWSTHSILAC NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 300
PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR 360
HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT 420
DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD 480
RVVLVNTSLG WPNGLALDYD EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL 540
LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS 600
HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG 660
VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY 720
WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG 780
SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ 840
YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC 900
SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID EQQSPDIILP 960
IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF TVVVSSVPSQ NLEIQPYDLS 1020
IDIYSRYIYW TCEATNVINV TRLDGRSVGV VLKGEQDRPR AVVVNPEKGY MYFTNLQERS 1080
PKIERAALDG TEREVLFFSG LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE 1140
DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 1200
EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGE 1260
IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK 1320
NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD CSDKSDELDC YPTEEPAPQA TNTVGSVIGV 1380
IVTIFVSGTV YFICQRMLCP RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS 1440
RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 1500
EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDL 1560
NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS 1613 
Gene Ontology
 GO:0009986; C:cell surface; IDA:BHF-UCL.
 GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL.
 GO:0005769; C:early endosome; IEA:Compara.
 GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0043025; C:neuronal cell body; IBA:RefGenome.
 GO:0005886; C:plasma membrane; IDA:BHF-UCL.
 GO:0043235; C:receptor complex; IBA:RefGenome.
 GO:0045202; C:synapse; IBA:RefGenome.
 GO:0034185; F:apolipoprotein binding; IBA:RefGenome.
 GO:0071936; F:coreceptor activity involved in Wnt receptor signaling pathway; IDA:BHF-UCL.
 GO:0019210; F:kinase inhibitor activity; IMP:BHF-UCL.
 GO:0005041; F:low-density lipoprotein receptor activity; IDA:MGI.
 GO:0019534; F:toxin transporter activity; IMP:BHF-UCL.
 GO:0042813; F:Wnt-activated receptor activity; IBA:RefGenome.
 GO:0090245; P:axis elongation involved in somitogenesis; IBA:RefGenome.
 GO:0060349; P:bone morphogenesis; IBA:RefGenome.
 GO:0046849; P:bone remodeling; IBA:RefGenome.
 GO:0060444; P:branching involved in mammary gland duct morphogenesis; IBA:RefGenome.
 GO:0061310; P:canonical Wnt receptor signaling pathway involved in cardiac neural crest cell differentiation involved in heart development; IEA:Compara.
 GO:0044335; P:canonical Wnt receptor signaling pathway involved in neural crest cell differentiation; IC:BHF-UCL.
 GO:0061324; P:canonical Wnt receptor signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation; IEA:Compara.
 GO:0044340; P:canonical Wnt receptor signaling pathway involved in regulation of cell proliferation; IC:BHF-UCL.
 GO:0042074; P:cell migration involved in gastrulation; IEA:Compara.
 GO:0071397; P:cellular response to cholesterol; IMP:BHF-UCL.
 GO:0021587; P:cerebellum morphogenesis; IBA:RefGenome.
 GO:0021795; P:cerebral cortex cell migration; IEA:Compara.
 GO:0021987; P:cerebral cortex development; IBA:RefGenome.
 GO:0060026; P:convergent extension; IBA:RefGenome.
 GO:0071542; P:dopaminergic neuron differentiation; IEA:Compara.
 GO:0048596; P:embryonic camera-type eye morphogenesis; IBA:RefGenome.
 GO:0042733; P:embryonic digit morphogenesis; IEA:Compara.
 GO:0035115; P:embryonic forelimb morphogenesis; IEA:Compara.
 GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Compara.
 GO:0030326; P:embryonic limb morphogenesis; IBA:RefGenome.
 GO:0009880; P:embryonic pattern specification; IBA:RefGenome.
 GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IBA:RefGenome.
 GO:0035261; P:external genitalia morphogenesis; IBA:RefGenome.
 GO:0060325; P:face morphogenesis; IBA:RefGenome.
 GO:0021861; P:forebrain radial glial cell differentiation; IEA:Compara.
 GO:0021943; P:formation of radial glial scaffolds; IEA:Compara.
 GO:0001947; P:heart looping; IEA:Compara.
 GO:0060596; P:mammary placode formation; IEA:Compara.
 GO:0030901; P:midbrain development; IBA:RefGenome.
 GO:0030917; P:midbrain-hindbrain boundary development; IBA:RefGenome.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Compara.
 GO:0045599; P:negative regulation of fat cell differentiation; IEA:Compara.
 GO:2000151; P:negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis; IEA:Compara.
 GO:2000162; P:negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis; IEA:Compara.
 GO:2000168; P:negative regulation of planar cell polarity pathway involved in neural tube closure; IEA:Compara.
 GO:2000164; P:negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis; IEA:Compara.
 GO:2000166; P:negative regulation of planar cell polarity pathway involved in pericardium morphogenesis; IEA:Compara.
 GO:2000149; P:negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis; IEA:Compara.
 GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IMP:BHF-UCL.
 GO:0014029; P:neural crest formation; IDA:BHF-UCL.
 GO:0001843; P:neural tube closure; IBA:RefGenome.
 GO:0042475; P:odontogenesis of dentin-containing tooth; IBA:RefGenome.
 GO:0060021; P:palate development; IBA:RefGenome.
 GO:0003344; P:pericardium morphogenesis; IBA:RefGenome.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0045780; P:positive regulation of bone resorption; IEA:Compara.
 GO:0090263; P:positive regulation of canonical Wnt receptor signaling pathway; IDA:BHF-UCL.
 GO:0045787; P:positive regulation of cell cycle; IMP:BHF-UCL.
 GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Compara.
 GO:0045778; P:positive regulation of ossification; IEA:Compara.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:2000055; P:positive regulation of Wnt receptor signaling pathway involved in dorsal/ventral axis specification; IDA:BHF-UCL.
 GO:0036342; P:post-anal tail morphogenesis; IEA:Compara.
 GO:0090009; P:primitive streak formation; IBA:RefGenome.
 GO:0090118; P:receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport; IBA:RefGenome.
 GO:0060284; P:regulation of cell development; IEA:Compara.
 GO:0045598; P:regulation of fat cell differentiation; IBA:RefGenome.
 GO:0030278; P:regulation of ossification; IBA:RefGenome.
 GO:0051593; P:response to folic acid; IEA:Compara.
 GO:0007268; P:synaptic transmission; IBA:RefGenome.
 GO:0021794; P:thalamus development; IBA:RefGenome.
 GO:0060535; P:trachea cartilage morphogenesis; IBA:RefGenome.
 GO:0044332; P:Wnt receptor signaling pathway involved in dorsal/ventral axis specification; IDA:BHF-UCL.
 GO:0021874; P:Wnt receptor signaling pathway involved in forebrain neuroblast division; IEA:Compara.
 GO:0090244; P:Wnt receptor signaling pathway involved in somitogenesis; IBA:RefGenome. 
Interpro
 IPR011042; 6-blade_b-propeller_TolB-like.
 IPR000742; EG-like_dom.
 IPR023415; LDLR_class-A_CS.
 IPR000033; LDLR_classB_rpt.
 IPR002172; LDrepeatLR_classA_rpt.
 IPR017049; Low_density_Lipo_rcpt-rel_p5/6. 
Pfam
 PF00057; Ldl_recept_a
 PF00058; Ldl_recept_b 
SMART
 SM00181; EGF
 SM00192; LDLa
 SM00135; LY 
PROSITE
 PS00022; EGF_1
 PS01186; EGF_2
 PS50026; EGF_3
 PS01209; LDLRA_1
 PS50068; LDLRA_2
 PS51120; LDLRB 
PRINTS